tbuckley/cabot-search huggingface dataset:
COVID-19 pandemic impact on the oncology care using a virtual survey in Peru.
Authors: Guillermo Valencia, Daniel Enriquez, Patricia Rioja, Lizbeth Lachira, Monica Calderon, Jeannie Navarro-Vasquez, Silvia P. Neciosup, Tatiana Vidaurre
Journal: Journal of Clinical Oncology (2023)

e18738 Background: Advocacy programs in oncology has shown to improve outcomes through education, patient empowerment and civil society awareness, enabling better actions and efforts for patient care, especially in COVID-19 era. We present the results of a virtual survey conducted with the support of a Peruvian advocacy program for cancer patients in COVID-19 pandemic. Methods: In October 2020, a Peruvian Advocacy Program at Instituto Nacional de Enfermedades Neoplasicas (INEN) (“Club de la Mama”) formed by advocates and supported by a team of health professionals developed a virtual survey between October 2020 and July 2021 with the purpose of evaluating the impact of interruption of diagnosis or oncological treatment, detect a degree of anxiety/depression due to quarantine and provide information on the response of the oncological institution to the pandemic; from the patient’s perspective. This virtual survey includes: alternative treatment options, degree of anxiety/depression, early access to medical prescription, mode of appointment and quality of care. Patients answered the survey anonymously via web promoted on social networks (Facebook/ WhatsApp) and person-to-person diffusion. Results: A total of 244 patients were included, 78.7% females. Most of patients (86.5%) were from Lima and 86.9% had public insurance. 16.8% of patients had COVID-19 in the period of time evaluated. According to education level, 50.8% were superior, 37.7% high school, 10.7% elementary school and 0.8% illiterate. The most common cancer type was breast (36.1%), followed by hematologic (27.9%) and cervical (7.0%). The most common modality of care was in-person (73%), followed by telemedicine (15%) and only 2% not received medical consult. Regarding the degree of depression: 39% were mild, 14% moderate, 12% moderate-severe, 5% severe and 30% none. The most common degree of anxiety was 42% mild, 16% moderate, 12% severe, and 30% no degree. The most frequent reasons for not attending to hospital were unavailability of appointments (31%), followed by fear to COVID-19 (26%), geographic (10%) and difficulty in transportation (9.0%). The appointment cancellation/postponement time [reported in days] was: 18.0% not canceled, 16% [ &lt; 15], 14% [15-30], 19% [30-60], 10% [60-90], 23% [ &gt; 90]. Of the patients with surgical indication, 72% did not undergo surgery. Regarding prescription, 83% of patients received oncologic treatment, 10% did not received, and the remaining 7% answered that they did not need medication. Quality of care: 18% were considered excellent, 67% good, 10% fair, and 5% poor. Conclusions: Although the survey showed higher degrees of anxiety/depression in patients and longer cancellation/postponement/medication changes during COVID-19 pandemic, there was a significant adherence of medicine prescription, with no negative impact on the perception of quality of oncology care.
Epidemiology and outcomes of anorectal melanomas: A national database analysis.
Authors: Yating Wang, Qian Yu, Kevin Wei-Lun Chang, Leo Edward Reap, Howard R. Terebelo, Zhiyong Yu, Susan Elizabeth Lyons
Journal: Journal of Clinical Oncology (2023)

e21572 Background: Anorectal melanoma is a rare but aggressive type of melanoma, arising primarily from the mucosal epithelium from the anorectal tract. Knowledge of this rare etiology has been limited given its low incidence. This study aims to characterize the epidemiology and treatment outcomes of anorectal melanoma using a national database. Methods: The Surveillance, Epidemiology and End Results (SEER) Database was queried to identify patients with biopsy-proven anorectal melanoma. The following information was retrieved: tumor site, grade, stage, intervention, lymph node histology, and survival information for oncology codes as per the international classification of diseases. Statistical analysis was performed with Stata 15.1 (STATA Corp., College Station, TX, USA). Results: The age-adjusted anorectal melanoma annual incidence rates have been stable approximately 0.4-0.5 per 1 million from 2000 to 2019. Of the 823 biopsy-proven confirmed cases of anorectal melanoma from 2000 to 2018, 150 (18.2%) received chemotherapy, 182 (22.1%) received radiotherapy, 55 (6.7%) received chemoradiation, while 619 (75.2%) of the population received surgery alone or combined with chemotherapy and/or radiotherapy. Statistically significant improvement in survival was noted in treatment strategies that utilized surgery with and without chemotherapy and/or radiotherapy (median survival time 22 vs 9 months, p &lt; 0.0001). Patients with positive regional lymph nodes on pathology were associated with worse prognosis (median survival time 15 vs 37 months, p &lt; 0.0001). Outcomes did not differ based on sex (p = 0.810) and race (p = 0.372). Conclusions: Incidence of anorectal melanoma in the United States has been stable in the last twenty years. Treatment strategies including surgical resection should be adopted if possible to achieve improved survival outcomes.
Emerging phase 1 data of BLU-451 in advanced NSCLC with EGFR exon 20 insertions.
Authors: Danny Nguyen, Elaine Shum, Christina S Baik, Pasi A. Janne, Jyoti D. Patel, Erin Lynn Schenk, Yuji Shibata, Helena Alexandra Yu, Faris Albayya, Paul Pearson, Minjie Feng, Melinda Louie-Gao, Alena Zalutskaya, Alexander I. Spira
Journal: Journal of Clinical Oncology (2023)

9064 Background: In patients (pts) with NSCLC harboring EGFR exon 20 insertions (ex20ins), treatment options are limited, with platinum-based chemotherapy with/without programmed death-ligand 1 inhibitors being the standard of care in first line, and recent accelerated approvals of mobocertinib and amivantamab in the USA for second-line treatment. These second-line therapies have overall response rates of 28% and 40%, respectively, limited CNS activity, and are associated with AEs such as severe gastrointestinal AEs and edema. BLU-451 is an investigational, CNS-penetrant, potent, selective, and wild-type sparing EGFR tyrosine kinase inhibitor that is under investigation in the ongoing phase 1/2 CONCERTO trial (NCT05241873), including in pts with ex20ins. Methods: In phase 1 dose escalation using a 3+3 design, BLU-451 monotherapy was administered orally QD or BID and given in continuous 21-day cycles. The primary objectives include maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) determinations and safety. Key secondary objectives include antitumor activity, PK, and pharmacodynamics. Pts with EGFR ex20ins–positive NSCLC after prior platinum-based chemotherapy were enrolled. Prior ex20ins–targeted therapy and asymptomatic CNS disease were permitted. Tumor response was assessed per RECIST v1.1. Serial blood samples for analysis of BLU-451 PK and circulating tumor DNA (ctDNA) were collected. Results: As of Jan 20, 2023, 28 pts have been enrolled and dosed in 5 cohorts (100 mg–400 mg QD and 200 mg BID), including 19 (68%) pts with exon 20 insertions. The median number of prior systemic lines of therapy was 2.5 (range, 1–10), and 19/28 (68%) pts had prior ex20ins-targeted agents. The most common AEs were diarrhea (21%), cough (18%), fatigue (14%), pruritis (14%) and rash (14%); all were Grade 1 or 2. There were no dose-limiting toxicities. Partial responses, including a disappearance of a CNS target lesion, were seen, and early evidence of on-target activity with ctDNA reductions was observed. Conclusions: As of the data cutoff, BLU-451 monotherapy was generally well tolerated, with early evidence of clinical activity in heavily pretreated pts with EGFR ex20ins–positive NSCLC. Early data at initial dose levels consisted of tumor reduction including responses, CNS activity, and ctDNA responses. The dose escalation is ongoing to determine the MTD and/or RP2D. Clinical trial information: NCT05241873 .
Efficacy and safety of PD-1/PD-L1 inhibitor plus platinum-based chemotherapy vs. platinum-based chemotherapy alone in patients with previously untreated advanced large-cell neuroendocrine cancer of the lung.
Authors: Fengchun Mu, Bingjie Fan, Haoqian Li, Taotao Dong, Yueyuan Yao, Butuo Li, Chao Jiang, Linlin Wang
Journal: Journal of Clinical Oncology (2023)

9066 Background: Large-cell neuroendocrine carcinoma (LCNEC) is a rare tumor with a poor prognosis and limited treatment options. The efficacy of first-line therapies for LCNEC has not yet been established. This study evaluated the efficacy and safety of the combination of PD-1/PD-L1 inhibitor and platinum-based chemotherapy in treatment-naïve patients with advanced LCNEC. Methods: We retrospectively analyzed patients with advanced LCNEC who were treated with a PD-1/PD-L1 inhibitor plus platinum-based chemotherapy (PD-1/PD-L1 inhibitor group) or with platinum-based chemotherapy alone (chemotherapy group) based on data obtained from electronic databases of three participating cancer centers from January 2015 to August 2022. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were evaluated for each group. Safety was assessed in all patients who received at least one dose of their assigned treatment. Results: Among the 75 enrolled patients, 25 were allocated to receive PD-1/PD-L1 inhibitor plus platinum-based chemotherapy and 50 were allocated to receive platinum-based chemotherapy alone (patients were matched 1:2 on baseline characteristics). The median PFS was 15.1 months (95% confidence interval [CI], 7.1–23.2) in the PD-1/PD-L1 inhibitor group and 5.3 months (95% CI, 4.4–6.2) in the chemotherapy group (hazard ratio [HR], 0.26; 95% CI, 0.113–0.428; p &lt; 0.0001). The 12-month OS was 88.0% (95% CI, 67.7–96.9) in the PD-1/PD-L1 inhibitor group and 56.0% (95% CI, 41.4–69.7) in the chemotherapy group ( p = 0.0056). The ORRs in the two groups were 40% and 16%, respectively ( p = 0.022), and the DCRs were 96% and 70%, respectively ( p = 0.010). Regarding safety, the most common incidences of grade ≥ 3 adverse events involved neutropenia, leukopenia, anemia, and fatigue. There were no significant differences between the two groups. Immune-related adverse events (irAEs) in the PD-1/PD-L1 inhibitor group included cutaneous hemangiomas, hypothyroidism, anaphylaxis, and pneumonitis. Grade 3 or 4 irAEs were not observed. No new safety signals were noted. Conclusions: First-line PD-1/PD-L1 inhibitor plus platinum-based chemotherapy significantly improved PFS in patients with advanced LCNEC compared with platinum-based chemotherapy alone.
T cell exhaustion markers in multiple myeloma patients before and after physical activity intervention.
Authors: Janine Joseph, Michaela Hillengass, Joseph Tario, Kristopher Attwood, Adrienne Groman, Rikki A. Cannioto, Kirsten B. Moysich, Scott I Abrams, Jens Hillengass, Paul K Wallace
Journal: Journal of Clinical Oncology (2023)

8060 Background: There is substantial evidence that the immune system is dysfunctional in multiple myeloma (MM). Adaptive immune cells, such as CD4 + and CD8 + T cells, are ineffective at controlling MM progression, suggesting immunosuppression. Therefore, efforts to overcome immunosuppression are likely key to more effective tumor control. Recent evidence from pre-clinical models suggests that exercise represents a non-pharmaceutical means to reduce immune exhaustion, but few studies have examined the relationship between an exercise intervention and biomarkers of immune exhaustion in cancer patients, especially in MM – the objective of this study. Methods: In this feasibility trial, 24 MM patients participated in a six-month physical activity intervention. The strength training arm (n=12) performed twice weekly supervised resistance trainings. The walking arm (n=12) engaged in an unsupervised, home-based wearable activity tracker intervention. Subjects provided peripheral blood samples before the start and at the conclusion of the intervention. Comprehensive flow cytometry was utilized to assess the frequency of mononuclear cells of interest, including CD4 + and CD8 + T cells and subpopulations expressing the markers of exhaustion PD-1 and/or TIGIT, which are the two exhaustion markers with the highest expression in this study sample. Ratios of exhausted cells (expressing any, one, or both of those markers) to non-exhausted cells (expressing no exhaustion markers) were calculated. Changes in the median values of these ratios were compared using Wilcoxon signed-rank tests. Results: Results from the immune panels are shown for the combined sample (n=24). All ratios of exhausted to non-exhausted cells were lower at the end of the six-month intervention, compared to baseline. The ratio of CD4 + TIGIT + to non-exhausted CD4 + cells was significantly reduced, from 0.71 to 0.57 (p=0.04). The ratio of CD8 + PD-1 + to non-exhausted CD8 + cells was borderline significantly reduced, from 1.81 to 1.48 (p=0.06). Conclusions: This pilot study suggests that physical activity induces changes in MM patients’ immune systems, potentially rendering a less exhausted T cell state. Larger studies are warranted to examine how exercise alters activation vs exhaustion phenotypes within specific T cell subsets (naïve, central memory, effector memory, regulatory) and to elucidate the effects of strength-based vs aerobic exercise on T cell function. [Table: see text]
Metronomic dosing of selinexor in select soft tissue sarcomas (STS).
Authors: Aisha Alshibany, Abdulazeez Salawu, Abha A. Gupta, Esmail Mutahar Al-Ezzi, Sofia Genta, Eoghan Ruadh Malone, Geoffrey Alan Watson, Olga Vornicova, Lisa Wang, Limore Arones, Madeline J. Phillips, Jasmine Lee, Albiruni Ryan Abdul Razak
Journal: Journal of Clinical Oncology (2023)

11557 Background: Selinexor (S) is a first-in-class, oral, selective inhibitor of nuclear export (SINE). S has a demonstrated anti-tumor activity in STS. However, the use of S can be associated with toxicities, such as nausea, anorexia and fatigue. A modified dosing schedule may improve the tolerability of S without compromising its efficacy. Methods: We evaluated S when given metronomically in patients (pts) with advanced metastatic leiomyosarcoma, endometrial stromal sarcoma, and malignant peripheral nerve sheath tumors. S was administered daily for 4-days in a row followed by 3-days break, repeated weekly in a 28-days cycle. Dose levels (DL) were escalated using a 3+3 design to determine maximum tolerated dose. DL included 2.5mg (DL1), 5mg (DL2), 7.5mg (DL3), 10 mg (DL4), 12.5 mg (DL5), 15 mg (DL6) and 17.5 mg (DL7). S was administered until unacceptable toxicities or disease progression. Imaging was performed every 8 weeks. Primary objectives were safety and tolerability as well as the determination of the recommended phase II dose. Secondary objectives were anti-tumor activity, toxicity profile, and pharmacokinetics (PK) profile. Results: Twenty-five pts (22 females/3 males, median age 59 years [range 35-84]) were enrolled at different DL (3, 3, 4, 6, 6, 3 pts at DL1 to DL6 respectively). The most common adverse events (AE) of any grade were constipation (n = 11, 50%), nausea (n = 11, 50%), and dysgeusia (n = 10, 45%). Eight (36%) pts experienced G3/4 AE while on trial; most were hematological toxicities seen in 3 (14%) pts (anemia, neutropenia, and leukopenia, n = 1 each). Non-hematological G3/4 AE were seen in 5 (23%) pts (Including: colonic obstruction, atrial fibrillation, and spinal cord compression, n = 1 each). Two Dose limiting toxicities were experienced, at DL4 (thrombocytopenia) and DL5 (transaminitis). Twenty-two pts were evaluable for response; 10 (45%) pts had stable disease (SD) as best response. Eight pts with SD had disease stability of &gt; 4 months. Twelve pts (55%) had progressive disease. Median progression-free survival was 2.4 months (95% CI 1.7-5.3 months). PK data is awaiting final analysis. Conclusions: Metronomic S demonstrated tolerability in selected sarcoma pts. Signs of potential clinical benefit was seen in the form of SD. Further data comparison with historical controls and PK analysis are needed to put this finding into perspective. Clinical trial information: NCT04811196 .
Pilot randomized trial of a telehealth intervention for women with advanced ovarian cancer and PARP inhibitor-related fatigue.
Authors: Alexi A. Wright, Hanneke Poort, Anna Tavormina, Sarah Schmiege, Ursula A. Matulonis, Susana M Campos, Joyce F. Liu, Elizabeth Slivjak, Anna Gilmour, Julia Salinger, Ashley Ford Haggerty, Joanna J Arch
Journal: Journal of Clinical Oncology (2023)

e24122 Background: Poly(ADP-ribose) polymerase inhibitors (PARPi) have dramatically changed the treatment of advanced ovarian cancer and are increasingly used in other cancers. However, PARPi cause significant fatigue in nearly half of patients. Psychosocial interventions have shown promise for treating cancer-related fatigue, but there is limited evidence for use in patients with advanced cancers. Moreover, most fatigue interventions have been delivered in person over many sessions, limiting their accessibility and scalability. Methods: We conducted a pilot randomized trial of REVITALIZE, a 6-session telehealth intervention developed and refined by our group, compared with enhanced usual care among 35 fatigued patients with advanced or recurrent ovarian cancer on PARPi at two sites, Dana-Farber Cancer Institute and University of Pennsylvania. REVITALIZE was based on acceptance and commitment-based behavioral therapy and addressed modifiable contributors to PARPi-related fatigue. The trial tested the feasibility, acceptability, and preliminary efficacy of REVITALIZE through 3-month follow-up. Exit interviews were conducted with all REVITALIZE patients. Results: Among 35 participants (mean age=62.5 years, 83% stage III/IV disease, 46% first-line maintenance therapy), the trial met or exceeded its acceptability and feasibility goals. Exit interviews further indicated high acceptability. Relative to enhanced usual care, REVITALIZE significantly reduced fatigue interference at 12-week follow-up (Cohen’s d=.94, p=.008) and fatigue severity (d=.54, p=.049), while improving current fatigue levels (d=.62, p=0.04). REVITALIZE participants also reported improved fatigue self-efficacy, fatigue catastrophizing, depression, anxiety, and quality of life (ds=.60-.86). REVITALIZE participants were also numerically less likely to experience PARPi dose reductions compared with enhanced usual care (7% vs. 17%), and less likely to have dose delays (7% vs. 22%). Conclusions: Among fatigued adults with advanced ovarian cancer on PARPi, a brief telehealth intervention based on acceptance and commitment therapy showed strong feasibility, acceptability, and preliminary efficacy with improvements in fatigue, anxiety, depression, and quality of life outcomes. REVITALIZE is a novel, scalable telehealth intervention worthy of further investigation in patients with advanced cancers with PARPi-related fatigue. The study is supported by the National Comprehensive Cancer Network (NCCN) through a grant provided by AstraZeneca. Neither NCCN or AstraZeneca are the sponsors of this study. Clinical trial information: NCT04525183 .
Patterns of weight change and overall survival (OS) during first-line pembrolizumab treatment in patients with non-small cell lung cancer (NSCLC).
Authors: Mingjia Li, Songzhu Zhao, Kenneth Chian, Hyunwoo Kwon, Nicholas Jones, Adam Khorasanchi, Timothy Gauntner, Christopher C. Coss, Mitch A. Phelps, Daniel Spakowicz, Lai Wei, Asrar Alahmadi, Regan Michelle Memmott, Jacob Kaufman, Kai He, Peter G. Shields, David Paul Carbone, Gregory Alan Otterson, Carolyn J Presley, Dwight Hall Owen
Journal: Journal of Clinical Oncology (2023)

e21094 Background: Cancer-associated cachexia and weight change from treatment-related side effects profoundly influence treatment outcomes for patients with NSCLC. Limited data are available to compare the association between weight change and OS for patients with NSCLC treated with pembrolizumab alone or combined with chemotherapy. Therefore, we evaluated the change in weight after the first cycle of pembrolizumab-based treatments and its association with OS in patients with metastatic NSCLC. Methods: This retrospective study included 306 patients with NSCLC treated with a first line pembrolizumab-based regimen at Ohio State University from 2018-2021. Baseline characteristics were collected within seven days before cycle one treatment. Percent of weight change (PWC) was calculated as (cycle two weight – baseline weight)/baseline weight x 100%. Severe weight loss was defined as ≥75 th percentile (PWC ≤-3.5%). Kruskal Wallis test was used to compare the significance of median PWC between treatment groups. Cox proportional-hazards models were used to test associations with survival. Results: The median age was 64.0 (IQR 56.7-72.6) years. The median baseline BMI was 26.1 (IQR 22.4-30.7). There was no difference between the median PWCs of patients treated with pembrolizumab monotherapy (-1.2%, IQR -3.7-0.8%) vs. pembrolizumab with chemotherapy (-1.0%, IQR -3.4-0.6%), p = 0.587. The patients whose weight remained stable (PWC -1% to 1%, n = 87 (28.4%)) had the highest median OS at 45.6 months (95% CI 27.6 – not reached); while those with severe weight loss (PWC ≤-3.5%, n = 78 (25.5%)) and weight gain (PWC ≥1%, n = 65 (21.2%)) had significantly decreased survival with median OS 15.6 (95% CI 9.3-20.9) and 16.3 (95% CI 10.1-25.6) months respectively, overall model p-value &lt; 0.001. The PWC remained significantly associated with OS after adjusting for performance status, PD-L1, and treatment with p &lt; 0.001 (Table 1). Conclusions: For patients with metastatic NSCLC treated with first line pembrolizumab-based regimen, similar PWCs were seen between patients treated with pembrolizumab alone or combined with chemotherapy. Regardless of treatment, weight gain and severe weight loss after the first cycle of treatment were associated with reduced OS. Further in-depth analysis is warranted to investigate the potential causes of weight changes, especially for patients with positive PWC. [Table: see text]